Molecular solutions
parkinson's disease is a condition in which the limbs lose the coordination of involuntary movements. Muhammad Ali, the former heavy weight world boxing champion, is among the most famous of its victims. It is caused by a deficiency in the level of dopamine - a neuro-transmitter molecule in the brain. On the other hand, an excess of dopamine can be lead to certain types of schizophrenia, a psychotic mental illness often characterised by hallucinations and delusions due to a breakdown in the relation between thoughts, feelings and actions. The need to understand how dopamine levels are regulated in the body is very important.
A team of researchers from the Karolinska Institute, Stockholm, have reported that a key protein called Nurr 1 (nurr for nuclear receptor) is essential in the determination of dopamine-producing nerve cells in the embryo.Moreover, Nurr-1 may help in keeping dopamine cells active during adulthood ( Science , Vol 276, No 5310).
The starting point was a discovery made five years back by another group of scientists. They had reported that among the molecules that bind hormones and regulate gene expression in mouse tissue, there was one - Nurr-1 - that was restricted to the brain. Using sophisticated techniques of molecular biology, researchers at Stockholm proceeded to develop a strategy that would enable them to 'knock-out' the piece of dna that encoded the Nurr-1 gene. This is the standard approach to uncover the function of a gene that is known only in terms of a protein that it encodes.
Ordinarily, every gene exists in two copies. It was noted that laboratory mice lacking both copies of the Nurr-1 gene failed to suckle and died a day after birth. There was one essential difference between these mice and the normal ones: the ones without Nurr-1 showed a poorly organised mid-brain; the region that contains the dopamine-containing neurons implicated in Parkinson's disease. Further, mice lacking just one copy of the Nurr-1 gene appeared to undergo normal development but did not make as much dopamine as normal mice. The suggestion, yet to be tested, is that Nurr-1 enables dopamine-containing cells to develop and also causes them to produce the correct amounts of dopamine.
Exciting as this finding is, there is a long way to go before it can be translated into a therapy for patients of Parkinson's disease. Firstly, the precise molecular pathway between the functioning of Nurr-1 and dopamine production will need to be elucidated. Secondly, the interactions between Nurr-1 and other genes has to be understood in detail. And finally, the effectiveness of Nurr-1 based therapy in the bulk of Parkinson's disease patients will have to be ascertained. But the most important question will be how to administer the therapy.